Objective To develop a reversed-phase high-performance liquid chromatography(RP-HPLC) method for the determination of adipic acid dihydrazide(ADH) residues in the bulk of typhoid Vi polysaccharide-protein conjugate vaccine,and to optimize,verify and preliminarily apply the method,so as to use it for the determination of ADH residues in typhoid Vi polysaccharide-protein conjugate vaccine bulk or other conjugate vaccines.Methods RP-HPLC was used to detect ADH residues in the bulk of typhoid Vi polysaccharide-protein conjugate vaccine.The detection wavelength(full wavelength),mobile phase(10 mmol/L PBS(pH 7.0)+10% acetonitrile,10 mmol/L PBS(pH 7.0)+0.8% sodium chloride solution+10%methyl alcohol+5 mmol/L ammonium acetate solution) and flow rate(0.8 and 1.0 mL/min) were optimized.The method was then verified for the specificity,linear range,accuracy and precision,and determined for the limit of detection(LOD) and limit of quantitation(LOQ).The ADH residues in three batches of typhus Vi polysaccharide-protein conjugate vaccine bulks were detected by the established method.Results The optimum detection wavelength was determined to be 202 nm,the mobile phase was 10 mmol/L PBS(pH 7.0)+0.8% sodium chloride solution+10% methyl alcohol+5 mmol/L ammonium acetate solution,and the flow rate was 1.0 mL/min.This method could specifically determine ADH residues in conjugate bulk,and other components in conjugate vaccine bulk exhibited no interference to the detection of ADH peak.At the range of 2-10 μg/mL,ADH concentration in the reference solution showed a good linear correlation with the peak area,with the linear regression equation of y=30 617 x+1 296.5,R2=0.999 7.The spiked recovery rates of ADH in the bulks of typhoid Vi polysaccharide-protein conjugate vaccines were 91.70%-106.00%.The RSDs of precision verification were less than 8%.The LOD and LOQ were 0.2 and 0.5 μg/mL,respectively.ADH residues were not detected in the bulks of three batches of typhoid Vi polysaccharide-protein conjugate vaccines.Conclusion The developed method has good specificity,precision and accuracy with convenience and rapidity,which can be used for the determination of ADH residues in the bulk of typhoid Vi polysaccharide-protein conjugate vaccine.

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.

In order to provide the "guiding principles of clinical research on mild cognitive impairment (MCI) (protocol)" edited by Beijing United Study Group on MCI of the Capital Foundation of Medical Developments (CFMD) with evidence support, clinical criteria, subtypes, inclusion and exclusion of MCI, and use of rating scales were reviewed. The authors suggested that MCI clinical criteria and new diagnosis procedure from the MCI Working Group of the European Alzheimer's disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Diagnostic rating scales including Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Instrumental Activities of Daily Living (IADL) are very useful in definition of MCI but can not replace its clinical criteria. Absence of major repercussions on daily life in patients with MCI was emphasized, but the patients may have minimal impairment in complex IADL. According to their previous research, the authors concluded that highly recommendable neuropsychological scales with cut-off scores in the screening of MCI cases should include Mini-Mental State Examination (MMSE), logistic memory test such as Delayed Story Recall (DSR), executive function test such as Clock Draw Test (CDT), language test such as Verbal Category Fluency Test (VCFT), etc. And finally, the detection of biological and neuroimaging changes, including atrophy in hippocampus or medial temporal lobe in patients with MCI, was introduced.